Congestive heart failure affects over 4 million people in the United States and is the most common cause of hospitalization for patients over the age of 65. A leading cause of congestive heart failure is dilated cardiomyopathy. This condition is characterized by the progressive expansion of the heart muscle and an accompanying inability to maintain adequate blood flow. Patients typically complain of fatigue, shortness of breath and chest pain. There is presently no cure for this condition and up to 50% of patients die or require a heart transplant within 5 years of diagnosis.
A model of dilated cardiomyopathy has been generated in mice by mutating CREB, a gene involved in regulating the growth and development of cardiac muscle (www.UC hospitals.edu/news/IDC.mouse.html). This model should provide a means for scientists to study disease progression and to test various therapeutic approaches. The present invention is based upon the discovery that mutations in a different gene are also involved in the development of dilated cardiomyopathy and that mice that underexpress this gene provide a distinct model of the disease. Previous studies have described a similar gene, the relA-associated inhibitor (RAI), gene in yeast and humans (Yang, et al., J. Biol. Chem. 274:15662–15670 (1999); WO 0032628). Because the newly identified gene encodes a protein that is homologous to p53 binding protein 2, it has been designated as the “p53 binding protein-related protein” (PRP) gene.